Alzheimer's disease (AD) is associated with the accumulation of amyloid-β (Aβ), which accelerates cell senescence in human neural stem cells (NSCs). This study demonstrates that Aβ enhances senescence markers such as p16 and p21 expression, increases SA-β-gal activity, and activates the DNA damage response in NSCs. Aβ also suppresses SIRT1, a protein involved in regulating aging and downstream pathways like PGC-1α and FOXO3. Overexpression of SIRT1 significantly reduces Aβ-induced senescence in NSCs, suggesting SIRT1 as a potential therapeutic target for age-related neurodegenerative diseases. The study used human NSCs derived from induced pluripotent stem cells and employed various techniques including Western blot, immunofluorescence, and ROS detection to assess the effects of Aβ and SIRT1 on NSC senescence. Results indicate that Aβ accelerates NSC senescence, which may contribute to cognitive decline in AD. The findings highlight the role of SIRT1 in mitigating Aβ-induced senescence and suggest that targeting SIRT1 could be a promising strategy for treating AD.Alzheimer's disease (AD) is associated with the accumulation of amyloid-β (Aβ), which accelerates cell senescence in human neural stem cells (NSCs). This study demonstrates that Aβ enhances senescence markers such as p16 and p21 expression, increases SA-β-gal activity, and activates the DNA damage response in NSCs. Aβ also suppresses SIRT1, a protein involved in regulating aging and downstream pathways like PGC-1α and FOXO3. Overexpression of SIRT1 significantly reduces Aβ-induced senescence in NSCs, suggesting SIRT1 as a potential therapeutic target for age-related neurodegenerative diseases. The study used human NSCs derived from induced pluripotent stem cells and employed various techniques including Western blot, immunofluorescence, and ROS detection to assess the effects of Aβ and SIRT1 on NSC senescence. Results indicate that Aβ accelerates NSC senescence, which may contribute to cognitive decline in AD. The findings highlight the role of SIRT1 in mitigating Aβ-induced senescence and suggest that targeting SIRT1 could be a promising strategy for treating AD.